tbuckley/cabot-search huggingface dataset:
Glutathione peroxidase 8 expression on cancer cells and cancer‐associated fibroblasts facilitates lung cancer metastasis
Authors: Yu‐Lian Xu, Luo‐Wei Yuan, Xiao‐Ming Jiang, Min‐Xia Su, Mu‐Yang Huang, Yu‐Chi Chen, Le‐Le Zhang, Xiuping Chen, Hong Zhu, Jin‐Jian Lu
Journal: MedComm (2022)

Abstract Lung cancer is the leading cause of cancer death worldwide, of which lung adenocarcinoma (LUAD) is the most common subtype. Metastasis is the major cause of poor prognosis and mortality for lung cancer patients, which urgently needs great efforts to be further explored. Herein, glutathione peroxidase 8 (GPX8) was identified as a novel potential pro‐metastatic gene in LUAD metastatic mice models from GEO database. GPX8 was highly expressed in tumor tissues, predicting poor prognosis in LUAD patients. Knockdown of GPX8 inhibited LUAD metastasis in vitro and in vivo, while it did not obviously affect tumor growth. Knockdown of GPX8 decreased the levels of p‐FAK and p‐Paxillin and disturbed the distribution of focal adhesion. Furthermore, GPX8 was overexpressed in cancer‐associated fibroblast (CAF) and associated with CAF infiltration in tumor microenvironment of lung cancer. GPX8 silence on fibroblasts suppressed lung cancer cell migration in the coculture system. BRD2 and RRD4 were the potential transcriptionally regulators for GPX8. Bromodomain extra‐terminal inhibitor JQ1 downregulated GPX8 expression and suppressed lung cancer cell migration. Our findings indicate that highly expressed GPX8 in lung cancer cells and fibroblasts functions as a pro‐metastatic factor in lung cancer. JQ1 is identified as a potential inhibitor against GPX8‐mediated lung cancer metastasis.
Underrecognition of Symptoms During Breast Radiotherapy—Reply
Authors: Reshma Jagsi, Kent A. Griffith
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Differentiation of crescent-forming kidney progenitor cells into podocytes attenuates severe glomerulonephritis in mice
Authors: Maria Elena Melica, Giulia Antonelli, Roberto Semeraro, Maria Lucia Angelotti, Gianmarco Lugli, Samuela Landini, Fiammetta Ravaglia, Gilda La Regina, Carolina Conte, Letizia De Chiara, Anna Julie Peired, Benedetta Mazzinghi, Marta Donati, Alice Molli, Stefanie Steiger, Alberto Magi, Niccolò Bartalucci, Valentina Raglianti, Francesco Guzzi, Laura Maggi, Francesco Annunziato, Alexa Burger, Elena Lazzeri, Hans-Joachim Anders, Laura Lasagni, Paola Romagnani
Journal: Science Translational Medicine (2022)

Crescentic glomerulonephritis is characterized by vascular necrosis and parietal epithelial cell hyperplasia in the space surrounding the glomerulus, resulting in the formation of crescents. Little is known about the molecular mechanisms driving this process. Inducing crescentic glomerulonephritis in two Pax2Cre reporter mouse models revealed that crescents derive from clonal expansion of single immature parietal epithelial cells. Preemptive and delayed histone deacetylase inhibition with panobinostat, a drug used to treat hematopoietic stem cell disorders, attenuated crescentic glomerulonephritis with recovery of kidney function in the two mouse models. Three-dimensional confocal microscopy and stimulated emission depletion superresolution imaging of mouse glomeruli showed that, in addition to exerting an anti-inflammatory and immunosuppressive effect, panobinostat induced differentiation of an immature hyperplastic parietal epithelial cell subset into podocytes, thereby restoring the glomerular filtration barrier. Single-cell RNA sequencing of human renal progenitor cells in vitro identified an immature stratifin-positive cell subset and revealed that expansion of this stratifin-expressing progenitor cell subset was associated with a poor outcome in human crescentic glomerulonephritis. Treatment of human parietal epithelial cells in vitro with panobinostat attenuated stratifin expression in renal progenitor cells, reduced their proliferation, and promoted their differentiation into podocytes. These results offer mechanistic insights into the formation of glomerular crescents and demonstrate that selective targeting of renal progenitor cells can attenuate crescent formation and the deterioration of kidney function in crescentic glomerulonephritis in mice.
Adenoviral-based vaccine promotes neoantigen-specific CD8 <sup>+</sup> T cell stemness and tumor rejection
Authors: Anna Morena D’Alise, Nadia Brasu, Carlo De Intinis, Guido Leoni, Valentina Russo, Francesca Langone, Denis Baev, Elisa Micarelli, Luca Petiti, Simone Picelli, Marwan Fakih, Dung T. Le, Michael J. Overman, Anthony F. Shields, Katrina S. Pedersen, Manish A. Shah, Sarbajit Mukherjee, Thea Faivre, Patricia Delaite, Elisa Scarselli, Luigia Pace
Journal: Science Translational Medicine (2022)

Upon chronic antigen exposure, CD8+ T cells become exhausted, acquiring a dysfunctional state correlated with the inability to control infection or tumor progression. In contrast, stem-like CD8+ T progenitors maintain the ability to promote and sustain effective immunity. Adenovirus (Ad)-vectored vaccines encoding tumor neoantigens have been shown to eradicate large tumors when combined with anti-programmed cell death protein 1 (αPD-1) in murine models; however, the mechanisms and translational potential have not yet been elucidated. Here, we show that gorilla Ad vaccine targeting tumor neoepitopes enhances responses to αPD-1 therapy by improving immunogenicity and antitumor efficacy. Single-cell RNA sequencing demonstrated that the combination of Ad vaccine and αPD-1 increased the number of murine polyfunctional neoantigen-specific CD8+ T cells over αPD-1 monotherapy, with an accumulation of Tcf1+ stem-like progenitors in draining lymph nodes and effector CD8+ T cells in tumors. Combined T cell receptor (TCR) sequencing analysis highlighted a broader spectrum of neoantigen-specific CD8+ T cells upon vaccination compared to αPD-1 monotherapy. The translational relevance of these data is supported by results obtained in the first 12 patients with metastatic deficient mismatch repair (dMMR) tumors vaccinated with an Ad vaccine encoding shared neoantigens. Expansion and diversification of TCRs were observed in post-treatment biopsies of patients with clinical response, as well as an increase in tumor-infiltrating T cells with an effector memory signature. These findings indicate a promising mechanism to overcome resistance to PD-1 blockade by promoting immunogenicity and broadening the spectrum and magnitude of neoantigen-specific T cells infiltrating tumors.
Leveraging reimbursement strategies to guide value-based adoption and utilization of medical AI
Authors: Kaushik P. Venkatesh, Marium M. Raza, James A. Diao, Joseph C. Kvedar
Journal: npj Digital Medicine (2022)

With the increasing number of FDA-approved artificial intelligence (AI) systems, the financing of these technologies has become a primary gatekeeper to mass clinical adoption. Reimbursement models adapted for current payment schemes, including per-use rates, are feasible for early AI products. Alternative and complementary models may offer future payment options for value-based AI. A successful reimbursement strategy will align interests across stakeholders to guide value-based and cost-effective improvements to care.
The role of cigarette smoking in periodontal disease and treatment outcomes of dental implant therapy
Authors: Danae Anastasia Apatzidou
Journal: Periodontology 2000 (2022)

Abstract Tobacco smoking has been implicated in periodontal pathology through various mechanisms, including perturbations of the inflammatory and host responses to putative periodontal pathogens, alterations in the subgingival microbial communities, and a compromised healing potential of the tissues leading to imbalance of tissue homeostasis. This review provides the evidence for the relationship between cigarette smoking and periodontal disease in an attempt to explain possible mechanisms of how tobacco smoking may exert its negative effects on the periodontal tissues via systemic and localized pathways. Early and more recent studies explore cigarette smoking–induced changes in periodontal clinical indices; in subgingival microbial flora by employing traditional detection methods for selected microorganisms, in addition to modern techniques such as deep sequencing and bioinformatics analyses that are able to fully characterize the microbial communities; and in inflammatory and immune responses critically appraising study limitations and differences in study protocol designs. Periodontal treatment outcomes and implant therapy outcomes are reviewed in an attempt to shed light on possible mechanisms for the inferior treatment outcome noted in smokers. The potential harmful effects of passive smoking are also reviewed, providing evidence for the advantages of smoking cessation. Quitting cigarette smoking should be recommended by the dentist, and effort should be made to inform smokers about the negative effects of smoking on the periodontal status and implant therapy outcomes.
Monoporous Microsphere as a Dynamically Movable Drug Carrier for Osteoporotic Bone Remodeling
Authors: Yawu Li, Yao Zha, Weikang Hu, Jia Chen, Shuaibing Liu, Shengmin Zhang, Jianglin Wang
Journal: Advanced Healthcare Materials (2022)

To repair systematically osteoporotic bone defects, it is important to make an effort to both diminish osteoporosis and enhance bone regeneration. Herein, a specifically monoporous microsphere (MPM) carrier encapsulating dosage-sensitive and short half-time parathyroid hormone (PTH) is constructed to tackle the issue. Compared with conventional microsphere carriers involving compact, porous, and mesoporous microspheres, the MPM is desirable to achieve precisely in situ delivery and to minimize topical accumulation. The findings show that the PTH loaded inside MPMs can be gradually released from the single hole of MPMs to improve the initial drug concentration. Also, the MPMs can self-shift with the daily movement of experimental animals to effectively reduce the topical aggregation of released drugs in vitro. In vivo evaluation further confirms that the implant of MPMs-PTH plays a dual role in stimulating the regenerative repair of the cranial defect and relieving osteoporosis in the whole body. Consequently, the current work develops a dynamically movable drug delivery system to achieve precisely in situ delivery, minimize topical accumulation, and systematically repair osteoporotic bone defects.
Perpetual observational studies: new strategies to support efficient implementation of observational studies and randomized trials in infectious diseases
Authors: Nasreen Hassoun-Kheir, C. Henri van Werkhoven, Jake Dunning, Thomas Jaenisch, Janko van Beek, Julia Bielicki, Christopher C. Butler, Bruno Francois, Stephan Harbarth, Ana C. Hernandez Padilla, Peter Horby, Marion Koopmans, James Lee, Jesús Rodriguez-Baño, Evelina Tacconelli, Yrene Themistocleous, Alike W. van der Velden, Marc Bonten, Herman Goossens, Marlieke E.A. de Kraker
Journal: Clinical Microbiology and Infection (2022)
The telomere maintenance mechanism spectrum and its dynamics in gliomas
Authors: Sojin Kim, Tamrin Chowdhury, Hyeon Jong Yu, Jee Ye Kahng, Chae Eun Lee, Seung Ah. Choi, Kyung-Min Kim, Ho Kang, Joo Ho Lee, Soon-Tae Lee, Jae-Kyung Won, Kyung Hyun Kim, Min-Sung Kim, Ji Yeoun Lee, Jin Wook Kim, Yong-Hwy Kim, Tae Min Kim, Seung Hong Choi, Ji Hoon Phi, Young-Kyoung Shin, Ja-Lok Ku, Sungyoung Lee, Hongseok Yun, Hwajin Lee, Dokyoung Kim, Kyoungmi Kim, Junho K. Hur, Sung-Hye Park, Seung-Ki Kim, Chul-Kee Park
Journal: Genome Medicine (2022)

The activation of the telomere maintenance mechanism (TMM) is one of the critical drivers of cancer cell immortality. In gliomas, TERT expression and TERT promoter mutation are considered to reliably indicate telomerase activation, while ATRX mutation and/or loss indicates an alternative lengthening of telomeres (ALT). However, these relationships have not been extensively validated in tumor tissues.
Sponge‐Like Macroporous Hydrogel with Antibacterial and ROS Scavenging Capabilities for Diabetic Wound Regeneration
Authors: Cheng Wei, Pengfei Tang, Youhong Tang, Laibao Liu, Xiong Lu, Kun Yang, Qingyuan Wang, Wei Feng, Quazi T. H. Shubhra, Zhenming Wang, Hongping Zhang
Journal: Advanced Healthcare Materials (2022)

Abstract Hydrogels with soft and wet properties have been intensively investigated for chronic disease tissue repair. Nevertheless, tissue engineering hydrogels containing high water content are often simultaneously suffered from low porous size and low water‐resistant capacities, leading to undesirable surgery outcomes. Here, a novel sponge‐like macro‐porous hydrogel (SM‐hydrogel) with stable macro‐porous structures and anti‐swelling performances is developed via a facile, fast yet robust approach induced by Ti 3 C 2 MXene additives. The MXene‐induced SM‐hydrogels (80% water content) with 200–300 µm open macropores, demonstrating ideal mass/nutrient infiltration capability at ≈20‐fold higher water/blood‐transport velocity over that of the nonporous hydrogels. Moreover, the highly strong interactions between MXene and polymer chains endow the SM‐hydrogels with excellent anti‐swelling capability, promising equilibrium SM‐hydrogels with identical macro‐porous structures and toughened mechanical performances. The SM‐hydrogel with versatile functions such as facilitating mass transport, antibacterial (bacterial viability in (Acrylic acid‐co‐Methacrylamide dopamine) copolymer‐Ti 3 C 2 MXene below 25%), and reactive oxygen species scavenging capacities (96% scavenging ratio at 120 min) synergistically promotes diabetic wound healing (compared with non‐porous hydrogels the wound closure rate increased from 39% to 81% within 7 days). Therefore, the durable SM‐hydrogels exhibit connective macro‐porous structures and bears versatile functions induced by MXene, demonstrating its great potential for wound tissue engineering.
Gut Dysbiosis Promotes Preeclampsia by Regulating Macrophages and Trophoblasts
Authors: Jiajia Jin, Liaomei Gao, Xiuli Zou, Yun Zhang, Zhijian Zheng, Xinjie Zhang, Jiaxuan Li, Zhenyu Tian, Xiaowei Wang, Junfei Gu, Cheng Zhang, Tiejun Wu, Zhe Wang, Qunye Zhang
Journal: Circulation Research (2022)

Background: Preeclampsia is one of the leading causes of maternal and perinatal morbidity and is characterized by hypertension, inflammation, and placental dysfunction. Gut microbiota plays key roles in inflammation and hypertension. However, its roles and mechanisms in preeclampsia have not been fully elucidated. Methods: 16S rRNA gene sequencing and targeted metabolomics were conducted on stool samples from 92 preeclamptic patients and 86 normal late-pregnant women. Then, fecal microbiota transplantation and in vitro and in vivo functional experiments were performed to explore the roles and mechanisms of gut microbiota in preeclampsia development. Results: We revealed the gut microbiota dysbiosis in preeclamptic patients, including significant reductions in short-chain fatty acid-producing bacteria and short-chain fatty acids. The gut microbiota of preeclamptic patients significantly exacerbated pathologies and symptoms of preeclamptic rats, whereas the gut microbiota of healthy pregnant women had significant protective effects. Akkermansia muciniphila , propionate, or butyrate significantly alleviated the symptoms of preeclamptic rats. Mechanistically, they significantly promoted autophagy and M2 polarization of macrophages in placental bed, thereby suppressing inflammation. Propionate also significantly promoted trophoblast invasion, thereby improved spiral arterial remodeling. Additionally, we identified a marker set consisting of Akkermansia , Oscillibacter , and short-chain fatty acids that could accurately diagnose preeclampsia. Conclusions: Our study revealed that gut microbiota dysbiosis is an important etiology of preeclampsia. Gut microbiota and their active metabolites have great potential for the treatment and diagnosis of preeclampsia. Our findings enrich the gut–placenta axis theory and contribute to the development of microecological products for preeclampsia.
Size-dependent activation of CAR-T cells
Authors: Qian Xiao, Xinyan Zhang, Liqun Tu, Jian Cao, Christian S. Hinrichs, Xiaolei Su
Journal: Science Immunology (2022)

As the targets of chimeric antigen receptor (CAR)-T cells expand to a variety of cancers, autoimmune diseases, viral infections, and fibrosis, there is an increasing demand for identifying new antigens and designing new CARs that can be effectively activated. However, the rational selection of antigens and the design of CARs are limited by a lack of knowledge regarding the molecular mechanism by which CARs are activated by antigens. Here, we present data supporting a "size exclusion" model explaining how antigen signals are transmitted across the plasma membrane to activate the intracellular domains of CARs. In this model, antigen engagement with CAR results in a narrow intermembrane space that physically excludes CD45, a bulky phosphatase, out of the CAR zone, thus favoring CAR phosphorylation by kinases, which further triggers downstream pathways leading to T cell activation. Aligned with this model, increasing the size of CAR extracellular domains diminished CAR-T activation both in vitro and in a mouse lymphoma model; membrane-proximal epitopes activated CAR-Ts better than membrane-distal epitopes. Moreover, increasing the size of CD45 by antibody conjugation enhanced the activation of CARs that recognize membrane-distal epitopes. Consistently, CAR-Ts expressing CD45RABC, the larger isoform, were activated to a higher level than those expressing a smaller isoform CD45RO. Together, our work revealed that CAR-T activation depends on the size difference between the CAR-antigen pair and CD45; the size of CAR, antigen, and CD45 can thus be targets for tuning CAR-T activation.
Noninvasive Fibrosis Screening in Fatty Liver Disease Among Vulnerable Populations: Impact of Diabetes and Obesity on FIB-4 Score Accuracy
Authors: Rebecca G. Kim, Jasmine Deng, Jewel N. Reaso, James P. Grenert, Mandana Khalili
Journal: Diabetes Care (2022)

Fatty liver disease (FLD) is prevalent in diabetes, and both disproportionately affect vulnerable populations. The FIB-4 index is recommended to screen for advanced liver fibrosis. Limited data have suggested that diabetes may impact FIB-4.We evaluated FIB-4 accuracy for advanced fibrosis compared with liver biopsy in the presence of diabetes and obesity.Among 363 FLD patients receiving care in San Francisco's safety net health care system from August 2009 to February 2020, characteristics were as follows: median age 51 years, 46% male, 59% Hispanic, 68% obese, 33% with diabetes, and 31% with advanced fibrosis on histology. Overall, the c-statistic for FIB-4 was 0.79, but was worse in patients with diabetes, 0.68, than without, 0.85 (P = 0.003). Accuracy also varied by weight, at 0.65, 0.85, and 0.75 for normal weight, overweight, and obese, respectively, although not significantly (P = 0.24).The findings highlight limitations of FIB-4 in screening for advanced liver fibrosis, particularly in individuals with diabetes.
Underrecognition of Symptoms During Breast Radiotherapy
Authors: Shijie Yang, Xiequn Xu
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Assessment of Accommodation Requests Reported by a National Sample of US MD Students by Category of Disability
Authors: Lisa M. Meeks, Karina Pereira-Lima, Melissa Plegue, Erene Stergiopoulos, Neera R. Jain, Amy Addams, Christopher J. Moreland
Journal: JAMA (2022)

Lisa M. Meeks, PhD; Melissa Plegue, MA; Ben Case, MPH; Bonnielin K. Swenor, PhD, MPH; Srijan Sen, MD, PhD
Pan-cancer integrative histology-genomic analysis via multimodal deep learning
Authors: Richard J. Chen, Ming Y. Lu, Drew F.K. Williamson, Tiffany Y. Chen, Jana Lipkova, Zahra Noor, Muhammad Shaban, Maha Shady, Mane Williams, Bumjin Joo, Faisal Mahmood
Journal: Cancer Cell (2022)

The rapidly emerging field of computational pathology has demonstrated promise in developing objective prognostic models from histology images. However, most prognostic models are either based on histology or genomics alone and do not address how these data sources can be integrated to develop joint image-omic prognostic models. Additionally, identifying explainable morphological and molecular descriptors from these models that govern such prognosis is of interest. We use multimodal deep learning to jointly examine pathology whole-slide images and molecular profile data from 14 cancer types. Our weakly supervised, multimodal deep-learning algorithm is able to fuse these heterogeneous modalities to predict outcomes and discover prognostic features that correlate with poor and favorable outcomes. We present all analyses for morphological and molecular correlates of patient prognosis across the 14 cancer types at both a disease and a patient level in an interactive open-access database to allow for further exploration, biomarker discovery, and feature assessment.
Long-term Survival After Endoscopic Resection For Gastric Cancer: Real-world Evidence From a Multicenter Prospective Cohort
Authors: Haruhisa Suzuki, Hiroyuki Ono, Toshiaki Hirasawa, Yoji Takeuchi, Kenji Ishido, Shu Hoteya, Tomonori Yano, Shinji Tanaka, Yosuke Toya, Masahiro Nakagawa, Takashi Toyonaga, Kenichi Takemura, Kingo Hirasawa, Mitsuru Matsuda, Hironori Yamamoto, Yosuke Tsuji, Satoru Hashimoto, Maeda Yuki, Tsuneo Oyama, Ryuta Takenaka, Yoshinobu Yamamoto, Yuji Naito, Katsumi Yamamoto, Nozomu Kobayashi, Yoshiro Kawahara, Masaaki Hirano, Shigeto Koizumi, Shinichiro Hori, Masahiro Tajika, Takuto Hikichi, Kenshi Yao, Chizu Yokoi, Ken Ohnita, Yasuhiro Hisanaga, Tetsuya Sumiyoshi, Shinji Kitamura, Hisao Tanaka, Ryo Shimoda, Taichi Shimazu, Kohei Takizawa, Satoshi Tanabe, Hitoshi Kondo, Hiroyasu Iishi, Motoki Ninomiya, Ichiro Oda
Journal: Clinical Gastroenterology and Hepatology (2022)